{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:44:48Z","timestamp":1781786688344,"version":"3.54.5"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100010753","name":"National Health Laboratory Service","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010753","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007112","name":"University of Cape Town","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007112","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001332","name":"Council\u00a0for\u00a0Scientific and Industrial Research, South Africa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regulatory Toxicology and Pharmacology"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1016\/j.yrtph.2019.104508","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T19:56:51Z","timestamp":1572292611000},"page":"104508","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["In vitro and in vivo toxicity evaluation of non-neuroleptic phenothiazines, antitubercular drug candidates"],"prefix":"10.1016","volume":"109","author":[{"given":"Sumayah","family":"Salie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Labuschagn\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avril","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohair","family":"Geyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar","family":"Jardine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7403-4604","authenticated-orcid":false,"given":"Muazzam","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-9839","authenticated-orcid":false,"given":"Nai-Jen","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yrtph.2019.104508_bib1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1475-2875-14-8","article-title":"Efficacy and pharmacokinetic evaluation of a novel anti-malarial compound (NP046) in a mouse model","volume":"14","author":"Abay","year":"2015","journal-title":"Malar. J."},{"key":"10.1016\/j.yrtph.2019.104508_bib2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/jac\/dkr500","article-title":"Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine","volume":"67","author":"Abbate","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ijantimicag.2009.12.019","article-title":"Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!","volume":"35","author":"Amaral","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"10.1016\/j.yrtph.2019.104508_bib4","first-page":"409","article-title":"Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB. In Vivo","volume":"24","author":"Amaral","year":"2010"},{"key":"10.1016\/j.yrtph.2019.104508_bib5","article-title":"Thioridazine: a non-antibiotic drug highly effective, in combination with first line anti-tuberculosis drugs, against any form of antibiotic resistance of Mycobacterium tuberculosis due to its multi-mechanisms of action","volume":"6","author":"Amaral","year":"2017","journal-title":"Antibiotics (Basel)"},{"key":"10.1016\/j.yrtph.2019.104508_bib6","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1590\/S1806-37132010000500017","article-title":"Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 2: second line drugs","volume":"36","author":"Arbex","year":"2010","journal-title":"J. Bras. Pneumol."},{"key":"10.1016\/j.yrtph.2019.104508_bib7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1128\/AAC.36.1.209","article-title":"In vitro activities of chloroquine in combination with chlorpromazine or prochlorperazine against isolates of Plasmodium falciparum","volume":"36","author":"Basco","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/BF00117862","article-title":"Relative cytotoxicity of psychotropic drugs in cultured rat hepatocytes","volume":"3","author":"Boelsterli","year":"1987","journal-title":"Cell Biol. Toxicol."},{"key":"10.1016\/j.yrtph.2019.104508_bib9","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2015.77","article-title":"Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and anticancer stem cell agent using public gene expression data","volume":"6","author":"Cheng","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.yrtph.2019.104508_bib10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1742-7843.2009.00417.x","article-title":"Chronic treatment with fluphenazine alters parameters of oxidative stress in liver and kidney of rats","volume":"105","author":"Corte","year":"2009","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"10.1016\/j.yrtph.2019.104508_bib11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tox.2015.02.004","article-title":"Cytotoxicity of phenothiazine derivatives associated with mitochondrial dysfunction: a structure-activity investigation","volume":"330","author":"de Faria","year":"2015","journal-title":"Toxicology"},{"key":"10.1016\/j.yrtph.2019.104508_bib12","series-title":"Drug-like Properties : Concepts, Structure Design and Methods : from ADME to Toxicity Optimization","author":"Di","year":"2016"},{"key":"10.1016\/j.yrtph.2019.104508_bib13","series-title":"Sprague Dawley Rats and Gottingen Minipigs. Regul Toxicol Pharmacol","first-page":"195","article-title":"Acute and subacute toxicity studies of CMICE-013, a novel iodinated rotenone-based myocardial perfusion tracer","volume":"vol. 80","author":"Duan","year":"2016"},{"key":"10.1016\/j.yrtph.2019.104508_bib14","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1128\/AAC.03408-14","article-title":"Sterilizing activity of thioridazine in combination with the first-line regimen against acute murine tuberculosis","volume":"58","author":"Dutta","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib15","doi-asserted-by":"crossref","first-page":"9896575","DOI":"10.1155\/2016\/9896575","article-title":"Potential antioxidant activity of new tetracyclic and pentacyclic nonlinear phenothiazine derivatives","volume":"2016","author":"Engwa","year":"2016","journal-title":"Biochem. Res. Int."},{"key":"10.1016\/j.yrtph.2019.104508_bib16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejps.2012.04.015","article-title":"Impact of FaSSIF on the solubility and dissolution-\/permeation rate of a poorly water-soluble compound","volume":"47","author":"Frank","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.yrtph.2019.104508_bib17","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1503\/cmaj.1040752","article-title":"Liver enzyme alteration: a guide for clinicians","volume":"172","author":"Giannini","year":"2005","journal-title":"CMAJ (Can. Med. Assoc. J.)"},{"key":"10.1016\/j.yrtph.2019.104508_bib18","first-page":"1105","article-title":"Mildly elevated liver transaminase levels in the asymptomatic patient","volume":"71","author":"Giboney","year":"2005","journal-title":"Am. Fam. Physician"},{"key":"10.1016\/j.yrtph.2019.104508_bib19","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.rmed.2006.01.014","article-title":"Side effects due to primary antituberculosis drugs during the initial phase of therapy in 1149 hospitalized patients for tuberculosis","volume":"100","author":"Gulbay","year":"2006","journal-title":"Respir. Med."},{"key":"10.1016\/j.yrtph.2019.104508_bib20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jep.2016.07.036","article-title":"Sub-acute and chronic toxicity profiles of Markhamia tomentosa ethanolic leaf extract in rats","volume":"193","author":"Ibrahim","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.yrtph.2019.104508_bib21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S1734-1140(12)70726-0","article-title":"Chemical structure of phenothiazines and their biological activity","volume":"64","author":"Jaszczyszyn","year":"2012","journal-title":"Pharmacol. Rep."},{"key":"10.1016\/j.yrtph.2019.104508_bib22","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09657","article-title":"The challenge of new drug discovery for tuberculosis","volume":"469","author":"Koul","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.yrtph.2019.104508_bib23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/cbf.1289","article-title":"Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats","volume":"25","author":"Kutlu","year":"2007","journal-title":"Cell Biochem. Funct."},{"key":"10.1016\/j.yrtph.2019.104508_bib24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.actatropica.2015.02.012","article-title":"Trypanothione reductase inhibitors: overview of the action of thioridazine in different stages of Chagas disease","volume":"145","author":"Lo Presti","year":"2015","journal-title":"Acta Trop."},{"key":"10.1016\/j.yrtph.2019.104508_bib25","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/RHU.0000000000000297","article-title":"Effect of antituberculous drugs on serum uric acid and urine uric acid excretion","volume":"21","author":"Louthrenoo","year":"2015","journal-title":"J. Clin. Rheumatol."},{"key":"10.1016\/j.yrtph.2019.104508_bib26","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1002\/hep.1840200610","article-title":"Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis","volume":"20","author":"Moradpour","year":"1994","journal-title":"Hepatology"},{"key":"10.1016\/j.yrtph.2019.104508_bib27","first-page":"1525","article-title":"What suits best for organ weight Analysis : review of relationship between organ weight and body\/brain weight for rodent toxicity studies","volume":"5","author":"Nirogi","year":"2014","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"10.1016\/j.yrtph.2019.104508_bib28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1006\/rtph.2000.1399","article-title":"Concordance of the toxicity of pharmaceuticals in humans and in animals","volume":"32","author":"Olson","year":"2000","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2019.104508_bib29","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0924-8579(02)00110-3","article-title":"Intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed Staphylococcus aureus","volume":"20","author":"Ordway","year":"2002","journal-title":"Int. J. Antimicrob. Agents"},{"key":"10.1016\/j.yrtph.2019.104508_bib30","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1128\/AAC.47.3.917-922.2003","article-title":"Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis","volume":"47","author":"Ordway","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002464","article-title":"Tuberculosis and HIV co-infection","volume":"8","author":"Pawlowski","year":"2012","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.yrtph.2019.104508_bib32","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1128\/AAC.25.5.571","article-title":"Antileishmanial activity of chlorpromazine","volume":"25","author":"Pearson","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib33","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1016\/j.ejmech.2011.05.013","article-title":"Recent progress in biological activities of synthesized phenothiazines","volume":"46","author":"Pluta","year":"2011","journal-title":"Eur. J. Med. Chem."},{"issue":"Suppl. 1","key":"10.1016\/j.yrtph.2019.104508_bib34","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1016\/j.ijmyco.2016.09.058","article-title":"Uric acid levels in patients on antituberculosis drugs in the Southwest region of Cameroon","volume":"5","author":"Pokam","year":"2016","journal-title":"Int. J. Mycobacteriol."},{"key":"10.1016\/j.yrtph.2019.104508_bib35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jceh.2012.12.001","article-title":"Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management","volume":"3","author":"Ramappa","year":"2013","journal-title":"J. Clin. Exp. Hepatol."},{"key":"10.1016\/j.yrtph.2019.104508_bib36","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1136\/bmj.1.5854.655","article-title":"Active chronic hepatitis after chlorpromazine ingestion","volume":"1","author":"Russell","year":"1973","journal-title":"Br. Med. J."},{"key":"10.1016\/j.yrtph.2019.104508_bib37","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000138232","article-title":"Toxicity of promazine and chlorpromazine to isolated rat hepatocytes and its modification by liposome entrapment","volume":"33","author":"Salhab","year":"1986","journal-title":"Pharmacology"},{"key":"10.1016\/j.yrtph.2019.104508_bib38","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1093\/jac\/dku036","article-title":"Novel non-neuroleptic phenothiazines inhibit Mycobacterium tuberculosis replication","volume":"69","author":"Salie","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib39","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1186\/s12879-016-1933-0","article-title":"Severe adverse events during second-line tuberculosis treatment in the context of high HIV Co-infection in South Africa: a retrospective cohort study","volume":"16","author":"Schnippel","year":"2016","journal-title":"BMC Infect. Dis."},{"key":"10.1016\/j.yrtph.2019.104508_bib40","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3746\/pnf.2015.20.3.190","article-title":"Acute and subacute oral toxicity evaluation of crude antifungal compounds produced by lactobacillus plantarum HD1 in rats","volume":"20","author":"Son","year":"2015","journal-title":"Prev. Nutr. Food Sci."},{"key":"10.1016\/j.yrtph.2019.104508_bib41","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1378\/chest.99.2.465","article-title":"Toxic hepatitis with isoniazid and rifampin. A meta-analysis","volume":"99","author":"Steele","year":"1991","journal-title":"Chest"},{"key":"10.1016\/j.yrtph.2019.104508_bib42","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/j.1365-2125.2007.03021.x","article-title":"Thioridazine: resurrection as an antimicrobial agent?","volume":"64","author":"Thanacoody","year":"2007","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.yrtph.2019.104508_bib43","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1128\/AAC.00749-08","article-title":"New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development","volume":"53","author":"van den Boogaard","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0924-8579(00)00343-5","article-title":"Enhancement of antibiotic activity against poly-drug resistant Mycobacterium tuberculosis by phenothiazines","volume":"17","author":"Viveiros","year":"2001","journal-title":"Int. J. Antimicrob. Agents"},{"key":"10.1016\/j.yrtph.2019.104508_bib45","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/jac\/dks483","article-title":"Antitubercular pharmacodynamics of phenothiazines","volume":"68","author":"Warman","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.yrtph.2019.104508_bib46","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1747-0285.2006.00391.x","article-title":"Searching for new antimalarial therapeutics amongst known drugs","volume":"67","author":"Weisman","year":"2006","journal-title":"Chem. Biol. Drug Des."},{"key":"10.1016\/j.yrtph.2019.104508_bib47","series-title":"Global Tuberculosis Report 2018","author":"World Health Organization","year":"2018"}],"container-title":["Regulatory Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230019302727?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230019302727?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T12:29:30Z","timestamp":1759494570000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0273230019302727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":47,"alternative-id":["S0273230019302727"],"URL":"https:\/\/doi.org\/10.1016\/j.yrtph.2019.104508","relation":{},"ISSN":["0273-2300"],"issn-type":[{"value":"0273-2300","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In vitro and in vivo toxicity evaluation of non-neuroleptic phenothiazines, antitubercular drug candidates","name":"articletitle","label":"Article Title"},{"value":"Regulatory Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yrtph.2019.104508","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104508"}}